Atlas of Genetics and Cytogenetics in Oncology and Haematology

Taking over the Atlas
Dear Colleagues,
The Atlas, once more, is in great danger, and I will have to proceed to a collective economic lay-off
of all the team involved in the Atlas before the begining of April 2015 (a foundation having suddenly
withdrawn its commitment to support the Atlas).
I ask you herein if any Scientific Society (a Society of Cytogenetics, of Clinical Genetics, of Hematology,
or a Cancer Society, or any other...), any University and/or Hospital, any Charity, or any database would be
interested in taking over the Atlas, in whole or in part. If taking charge of the whole lot is too big, a
consortium of various actors could be the solution (I am myself trying to find partners).
Could you please spread the information, contact the relevant authorities, and find partners.
Survival of the Atlas will be critically dependant upon your ability to find solutions (and urgently!).
Kind regards.
Jean-Loup Huret jlhuret@AtlasGeneticsOncology.orgDonations are also welcome
If each casual visitor gives 3 Euros or Dollars, the Atlas is saved in a week !
If each professional gives 100 Euros or Dollars once a year (now), the Atlas is saved in 2 weeks !
Don't let the Atlas imminent demise
Note: we send fiscal receipts for donations equal or above 50 Euros or Dollars

I.2. t-loops, G-loops, D-loops

Telomeres have a 3' G-rich overhang

A t-loop is formed when the single-stranded 3' strand is looped back and
anneals to the double-stranded hexamer repeats; as the G- rich strand displaces
one strand a D, or displacement loop, is created

t-loop formation confers some protection from exonucleases

I.3. Protein Components

Telomere binding proteins include:

I.3.1. TRF1 (telomeric repeat binding factor 1)

Expressed ubiquitously throughout the cell cycle

Binds to TTAGGG repeat as a homodimer (at t-loops) with great specificity

Functions in cis to inhibit telomerase-dependent elongation

Participates in regulation of the mitotic spindle

Regulated in turn by: TIN2, TANK1, TANK2 proteins (see below)

Negative regulator of telomere length (telomerase-dependent pathway)

Some data suggest a role for TRF1 in response to DNA double-stranded breaks

Potential role for PML NB in cellular differentiation, cell growth,
apoptosis, and an undefined role maintaining telomere integrity

III.2.7. Mechanism of ALT likely involves homologous recombination between
telomeres; sequences copied from a single telomere to another by complementary
annealing as a means of priming new telomeric DNA

V.3. Human Disorders of Premature Aging

Genetic aberrations that increase rates of telomere erosion and inhibit normal
DNA repair from occurring at the telomere synergize to cause premature aging,
a phenomenon seen in several disorders that feature predisposition to neoplasias.

VI.3. Chromosome and Genomic Instability

VI.3.1. Molecular and cytogenetic studies have indicated chromosomes with
even a single unprotected chromosome end are genetically unstable until
telomere integrity has been restored. During this period of genetic instability,
breakage-fusion-breakage (BFB) cycles occur, often culminating in chromosomal
aneuploidies

VI.3.3. During mitosis, separation of centromeres in dicentric chromosomes
to opposite poles produces an anaphase bridge, followed by chromosome breakage,
subsequent fusion of damaged ends, and promotion of additional BFB cycles

VI.3.4. Recurring cycles of gene amplification can arise during acquisition
of new telomeres by rearranged chromosomes, suggesting double-stranded DNA
breaks are important in promoting amplification of genes closest to a chromosomal
break

VI.3.5. In order to survive, genetically unstable cells also must escape
detection by cell-cycle regulators, such as p53, which can induce growth
arrest or apoptosis in response to damaged DNA

Critically shortened telomeres can be detected by p53

p53 binds to the G-rich, single-stranded overhang telomeric DNA and
also interacts with the t-loop

Loss of p53 function and telomere shortening work together to promote
tumorigenesis